Abstract Objective γ‐Aminobutyric acid (GABA) A ‐receptor subunit variants have recently been associated with neurodevelopmental disorders and/or epilepsy. The phenotype linked with each gene is becoming better known. Because of the common molecular structure and physiological role of these phenotypes, it seemed interesting to describe a putative phenotype associated with GABA A ‐receptor–related disorders as a whole and seek possible genotype–phenotype correlations. Methods We collected clinical, electrophysiological, therapeutic, and molecular data from patients with GABA A ‐receptor subunit variants (GABRA1, GABRB2, GABRB3, and GABRG2) through a national French collaboration using the EPIGENE network and compared these data to the one already described in the literature. Results We gathered the reported patients in three epileptic phenotypes: 15 patients with fever‐related epilepsy (40%), 11 with early developmental epileptic encephalopathy (30%), 10 with generalized epilepsy spectrum (27%), and 1 patient without seizures (3%). We did not find a specific phenotype for any gene, but we showed that the location of variants on the transmembrane (TM) segment was associated with a more severe phenotype, irrespective of the GABA A ‐receptor subunit gene, whereas N‐terminal variants seemed to be related to milder phenotypes. Significance GABA A ‐receptor subunit variants are associated with highly variable phenotypes despite their molecular and physiological proximity. None of the genes described here was associated with a specific phenotype. On the other hand, it appears that the location of the variant on the protein may be a marker of severity. Variant location may have important weight in the development of targeted therapeutics.
Notre approche experimentale a pour but d'evaluer le role de l'inflammation virale dans l'epileptogenese. Nous avons choisi de modeliser l'inflammation virale par injection d'un agoniste TLR-3, acide polyinosinique polycytidylique (PIC) soit intra-peritoneale, soit intra-hippocampique, Chaque modelisation inflammatoire etait couplee a un modele d'epileptogenese electrique le kindling rapide. L'ensemble de notre travail experimental etait realise chez le rat Wistar a P14 et a P75. Notre travail a montre que l'injection I. H, de PIC facilitait l'epileptogenese du cerveau immature et adulte et induisait une augmentation du taux I. H. D'IL-1P a P14 et P75. A l'oppose la minocycline inhibait cette facilitation de l'epileptogenese sans bloquer l'augmentation I. H. De l'IL-113 aux 2 âges etudies. Nous avons montre que l'injection I,p, de PIC facilitait l'epileptogenese du cerveau immature uniquement. Nous avons observe a P14 une reponse immunitaire avec une inflammation peripherique plus importante que chez l'adulte suivi d'une augmentation de l'IL-1s hippocampique presente uniquement a P14. La BHE avait une permeabilite plus importante chez les P14 pretraites par PIC que chez l'adulte. Ces elements nous amenent a suggerer un passage de rIL-1p de la peripherie vers le secteur intra-cerebral avec augmentation precoce et transitoire de l'IL-1s intra-hippocampique,enforcee que nous n'avons.
Abstract Objective Few studies have evaluated the efficacy of antiseizure medications (ASMs) according to the etiology of neonatal acute provoked seizures. We aimed to investigate the response to ASMs in term/near term neonates with acute arterial ischemic stroke (AIS), as well as the type of seizure at presentation and the monitoring approach. Methods We retrospectively evaluated neonates from 15 European level IV neonatal intensive care units who presented with seizures due to AIS and were monitored by continuous electroencephalography (cEEG) and/or amplitude‐integrated EEG (aEEG) in whom actual recordings, timing, doses, and response to ASMs were available for review. Results One hundred seven neonates were referred, and 88 were included. Of those, 56 met the criteria for evaluating the treatment response. The mean time to treatment was 7.9 h (SD = 16.4), and the most frequently administered first‐line ASM was phenobarbital (PB; 74/88, 84.1%). Seizures were controlled within 24 h from onset of symptoms in 64.3% (36/56) of neonates. Phenytoin (PHT) was effective in almost all neonates in whom it was trialed (24/25, 96.0%), whereas PB was effective in only 22.0% of patients (11/50). Infants treated with PB or PHT as first‐line treatment (53/56, 94.6%) showed a higher response rate with PHT (6/6, 100.0%) than with PB (11/47, 23.4%). Monitoring approach and seizure types were evaluated in 88 infants. Forty‐six of 88 (52.3%) were monitored with cEEG and 47.7% (42/88) with aEEG, with or without intermittent cEEG. The mean monitoring duration was 65.8 h (SD = 39.21). In 83 of 88 (94.3%) infants, the type of seizure suspected clinically prior to monitoring was confirmed afterward. Unilateral focal clonic seizures were seen in 71 of 88 infants (80.7%), whereas 11 of 88 (12.5%) presented with ictal apneas. Significance Our findings provide evidence in a large, homogenous cohort that PHT is more effective than PB in treating neonatal acute symptomatic seizures due to AIS.
